NM_207344.4:c.*6044T>C

Variant names:

• chr12-56475621-T-C
• rs1592275599
• NM_207344.4:c.*6044T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_207344.4(SPRYD4):​c.*6044T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPRYD4 NM_207344.4 3_prime_UTR
• Scores: Splicing: ADA: 0.04245
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.08
• Publications: 0 publications found

Genes affected

SPRYD4 (HGNC:27468): (SPRY domain containing 4) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

GLS2 (HGNC:29570): (glutaminase 2) The protein encoded by this gene is a mitochondrial phosphate-activated glutaminase that catalyzes the hydrolysis of glutamine to stoichiometric amounts of glutamate and ammonia. Originally thought to be liver-specific, this protein has been found in other tissues as well. Alternative splicing results in multiple transcript variants that encode different isoforms. [provided by RefSeq, Jul 2013]

ENSG00000285528 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 12-56475621-T-C is Benign according to our data. Variant chr12-56475621-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 681506.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207344.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRYD4	NM_207344.4	MANE Select	c.*6044T>C		3_prime_UTR	Exon 2 of 2	NP_997227.1	Q8WW59
	GLS2	NM_013267.4	MANE Select	c.929+3A>G		splice_region intron	N/A	NP_037399.2
	GLS2	NM_001280797.2		c.134+3A>G		splice_region intron	N/A	NP_001267726.1	A0A087X004

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPRYD4	ENST00000338146.7	TSL:1 MANE Select	c.*6044T>C		3_prime_UTR	Exon 2 of 2	ENSP00000338034.5	Q8WW59
	GLS2	ENST00000311966.9	TSL:1 MANE Select	c.929+3A>G		splice_region intron	N/A	ENSP00000310447.4	Q9UI32-1
	GLS2	ENST00000424141.6	TSL:1	n.*265+3A>G		splice_region intron	N/A	ENSP00000416282.2	A8K0A6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	15
DANN	Benign	0.95
PhyloP100		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.042
dbscSNV1_RF	Benign	0.23
SpliceAI score (max)		0.040		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1592275599; hg19: chr12-56869405;